Twentieth century has witnessed a blooming era for scientific community indulging in computational approaches for approximation of protein structures. Anfinsen in 1972 laid the foundation for protein structure prediction by correctly refolding ribonuclease molecule from its sequence [1]}. As stated in the paper, “the native conformation is determined by the totality of inter-atomic interactions and hence by the amino acid sequence in a given environment” [2]}. In other words, a protein attains its conformational nativity when its environment is at its lowest Gibbs free energy levels. Another statement put forward in their work was that a protein structure is only stable and functional in the environment it was chosen during natural selection. Despite knowing the physical environment requirement for folding a protein sequence, it remains a challenge to fold them into their functional form. Therefore, limiting the understanding of the sequence-structure-function paradigm [3]}, [4]}.
